L-deprenyl is a selective monamine oxidase B (MAO-B) inhibitor, which is widely used as an adjunct in the treatment of Parkinson's disease. While it's most common usage is for the treatment of Parkinson's disease, L-deprenyl was originally developed as an antidepressant agent. Recent testing has indicated that L-deprenyl may have some effect on increasing sexual response in aging mammals, and also may have some effect, as demonstrated in laboratory rodents in increasing the natural life span. However, to date L-deprenyl has only been medically approved by regulatory agencies for use as an adjunctive treatment for Parkinson's disease.
Hyperadrenocorticism (Cushing's syndrome) is a common endocrine disorder. Currently two main subtypes of hyperadrenocorticism are recognized. Functional adrenal neoplasia accounts for about 20% of all cases of hyperadrenocorticism and represents the only form of non-ACTH dependent disease. Functional adrenal neoplasia is characterized by elevated serum cortisol concentrations, decreased plasma ACTH levels, and lack of suppression of the elevated cortisol concentration following the administration of a high dose (0.1 mg/kg) of dexamethasone (see definition of HDDS test, below).
The remainder of cases result from excessive production of ACTH. This most commonly occurs with pituitary overproduction of ACTH (pituitary-dependent hyperadrenocorticism, PDH, Cushing's disease) as the result of hyperplasia or tumor formation. This patent application refers specifically to these cases of pituitary over-production of ACTH. Finally, other cases of ACTH-dependent disease occur when tumors in other parts of the body secrete ACTH. This disorder is very uncommon. PDH is characterized by elevated serum cortisol concentrations, normal to elevated plasma ACTH concentrations, and suppression of serum cortisol concentration in response to a high dose of dexamethasone.
Several subtypes of PDH may occur. ACTH is normally produced and secreted from a portion of the pituitary called the pars distalis (PD). ACTH secretion in the PD is stimulated by corticotropin releasing hormone (CRH). ACTH can also be secreted from the pars intermedia (PI). Secretion and regulation of ACTH from the PI is under negative control by dopamine. Furthermore, experimentally induced chronic dopamine inhibition unmasks CRH stimulated release of ACTH from the PD. This implies that disease in either the PI or PD that results in increased concentrations of ACTH, may be Controlled by increasing dopamine concentrations. It has been hypothesized that dopamine depletion may therefore play a role in PDH. Excessive ACTH secretion lead to bilateral adrenal hyperplasia and results in overproduction of the steroid hormone cortisol. High levels of cortisol lead to the clinical signs that typify the disorder: excessive water drinking and urination, weight gain, a pot-bellied appearance, thinning of the skin, and progressive loss of hair. In the long term, high levels of cortisol can lead to heart disease and diabetes While therapeutic guidelines for Cushing's disease are established, these treatments generally are designed to decrease the production of cortisol by the adrenal and do nothing to address the primary problem, excessive release of ACTH by the pituitary. In addition, established therapies for Cushing's are associated with a number of serious, sometimes fatal, side-effects such as Addison's disease.
There is therefore a continuing and real need for the development of medications which can effectively treat Cushing's disease (especially in human, canine, equine species) addressing the primary problem, namely excessive release of ACTH by the pituitary and by addressing the problem in a manner of treatment which does not cause serious side effects.
While L-deprenyl is a known compound, it has never before been used at any level to treat Cushing's disease.
Like most drugs, L-deprenyl can have diverse physiological effects which are completely dependent upon the dose administered. In accordance with the present invention, L-deprenyl can be used for successful methods of treatment for Cushing's disease providing that it is used at the dosage levels mentioned herein, and providing it is administered at the periodic intervals and for the length of time mentioned herein. Obviously, when different dosages and levels of treatment are used, the results expressed herein may not be achieved. In fact, at higher doses, adverse behavioral effects may be encountered.
It is a primary objective of the present invention to provide an effective treatment for Cushing's disease.
Another primary objective of the present invention is to provide a treatment for Cushing's disease, which not only effectively treats the disease, but does so by addressing the primary cause of the disease, namely excessive release of ACTH by the pituitary.
A yet further objective of the present invention is to provide a treatment for Cushing's disease which does not have the serious side effects often associated with established therapies, such as Addison's disease.
The method and means of accomplishing each of the above as well as other primary objectives of the present invention will be apparent from the detailed description which will follow hereinafter.